Histamine augments colonic secretion in guinea pig distal colon

1990 ◽  
Vol 258 (3) ◽  
pp. G432-G439 ◽  
Author(s):  
Y. Z. Wang ◽  
H. J. Cooke ◽  
H. C. Su ◽  
R. Fertel
Keyword(s):  
Short Circuit ◽  
Nordihydroguaiaretic Acid ◽  
Short Circuit Current ◽  
Intestinal Secretion ◽  
Distal Colon ◽  
H2 Antagonist ◽  
Colonic Secretion ◽  
Set Up ◽  
Colonic Transport

We tested the hypothesis that the role of histamine in the control of intestinal secretion is mediated by prostaglandins (PGs). The effects of histamine on ion transport were examined in muscle-stripped sheets of mucosa/submucosa set up in flux chambers. Histamine evoked a transient concentration-dependent increase in short-circuit current (Isc) that was reduced by the Cl- transport inhibitor bumetanide. Histamine also caused the release of PGE2. The Isc response to histamine was reduced by indomethacin and piroxicam, which block PG formation, but not by nordihydroguaiaretic acid, which prevents production of lipoxygenase products. 2-Methylhistamine, but not dimaprit, evoked a concentration-dependent increase in Isc. The Isc response to histamine was reduced by the H1-blocker pyrilamine, but not by the H2-antagonist cimetidine. In addition to its direct effect, histamine augmented the responses of endogenously released neurotransmitters with and without indomethacin and hexamethonium. Tetrodotoxin (TTX) reduced the Isc response to 10(-3) M histamine. In the presence of TTX, exogenous histamine amplified the responses to PGs, vasoactive intestinal polypeptide, 2-chloroadenosine, bethanechol, and carbachol. These results suggest that histamine acts at H1-receptors on cells within the gut to mediate intestinal Cl- secretion in part by releasing PGs and by augmenting the actions of endogenously released neurotransmitters. Our results indicate that histamine has a role in the regulation of colonic transport function.

Activation of KCNQ (KV7) K+ channels in enteric neurons inhibits epithelial Cl- secretion in mouse distal colon

2021 ◽  
Author(s):  
Andrew J. Nickerson ◽  
Trey S. Rottgen ◽  
Vazhaikkurichi M. Rajendran
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Therapeutic Benefit ◽  
Enteric Neurons ◽  
Intestinal Epithelial ◽  
Cell Monolayers ◽  
Neuronal Populations ◽  
Irritable Bowel

KV7 (KCNQ) K+ channels are expressed in many neuronal populations, and play an important role in regulating membrane potential by generating a hyper-polarizing K+ current and decreasing cell excitability. However, the role of KV7 channels in the neural regulation of intestinal epithelial Cl- secretion is not known. Cl- secretion in mouse distal colon was measured as a function of short circuit current (ISC), while pharmacological approaches were used to test the hypothesis that activation of KV7 channels in enteric neurons would inhibit epithelial Cl- secretion. Flupirtine, a non-selective KV7 activator, inhibited basal Cl- secretion in mouse distal colon and abolished or attenuated the effects of drugs that target various components of enteric neurotransmission, including tetrodotoxin (NaV channel blocker), Veratridine (NaV channel activator), Nicotine (nicotinic acetylcholine receptor agonist) and Hexamethonium (nicotinic antagonist). In contrast, flupritine did not block the response to epithelium-targeted agents VIP (endogenous VPAC receptor ligand) or carbachol (non-selective cholinergic agonist). Flupirtine inhibited Cl- secretion in both full-thickness and seromuscular-stripped distal colon (containing the submucosal, but not myenteric plexus), but generated no response in epithelial T84 cell monolayers. KV7.2 and KV7.3 channel proteins were detected by immunofluorescence in whole-mount preparations of the submucosa from mouse distal colon. ICA 110381 (KV7.2/7.3 specific activator) inhibited Cl- secretion comparably to flupirtine. We conclude that KV7 channel activators inhibit neurally-driven Cl- secretion in the colonic epithelium, and may therefore have therapeutic benefit in treating pathologies associated with hyper-excitable enteric nervous system, such as irritable bowel syndrome with diarrhea (IBS-D).

Effect ofE. coliheat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice

2001 ◽  
Vol 280 (2) ◽  
pp. G216-G221 ◽  
Author(s):  
Alan N. Charney ◽  
Richard W. Egnor ◽  
Jesline T. Alexander-Chacko ◽  
Valentin Zaharia ◽  
Elizabeth A. Mann ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Proximal Colon ◽  
Guanylyl Cyclase C ◽  
Ussing Chambers ◽  
Heat Stable ◽  
Deficient Mice ◽  
Colonic Transport

We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3−Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+absorption, lower net Cl−absorption, and a negative residual ion flux ( JR), indicating net HCO3−absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl−( Js→mCl) and decreased net Cl−flux ( JnetCl) accompanied by increases in short-circuit current ( Isc), potential difference (PD), and tissue conductance ( G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon Js→mCland JnetCl, Isc, PD, G, and JRsimilar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa.

H2 receptors mediate cyclical chloride secretion in guinea pig distal colon

1990 ◽  
Vol 258 (6) ◽  
pp. G887-G893 ◽  
Author(s):  
Y. Z. Wang ◽  
H. J. Cooke
Keyword(s):  
Guinea Pig ◽  
Chloride Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Chloride Ions ◽  
H2 Antagonist ◽  
H2 Receptors ◽  
Peak Increase

We tested the hypothesis that histamine mediates ion secretion in the guinea pig distal colon by stimulating H2 receptors on submucosal neurons. Serosal addition of histamine evoked a transient increase in short-circuit current (Isc) followed by recurrent cyclical increases in Isc. The transient phase of the response was examined previously and was not investigated in these studies. Histamine (1.5-2.5 x 10(-5) M) evoked a peak increase in Isc of 177 +/- 25 microA/cm2 at intervals of 5 min for 1-2 h. The duration of each recurrent cycle averaged 2.1 +/- 0.3 min. The H2 agonist dimaprit evoked recurrent cycles that had larger amplitudes than those caused by histamine. In the presence of histamine or dimaprit, the amplitude of the first cycle of the response was always less than subsequent cycles, regardless of the initial concentration. The cyclical responses to histamine, 2-methylhistamine, or dimaprit were unaltered by the H1 blocker pyrilamine, were reduced by the H2 antagonist cimetidine, and were abolished by the neuronal blocker tetrodotoxin. Blockade of prostaglandin formation with piroxicam did not prevent the recurrent cycles. The recurrent cycles were inhibited by the chloride transport blocker bumetanide and by removal of chloride ions. Our results demonstrate that histamine mediates prolonged cyclical chloride secretion in the guinea pig distal colon by activating H2 receptors on submucosal neurons involved in regulation of epithelial chloride transport.

Neuroimmune interactions: role for cholinergic neurons in intestinal anaphylaxis

1992 ◽  
Vol 263 (6) ◽  
pp. G847-G852 ◽  
Author(s):  
N. H. Javed ◽  
Y. Z. Wang ◽  
H. J. Cooke
Keyword(s):  
Short Circuit ◽  
Bovine Milk ◽  
Cholinergic Neurons ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Ach Release ◽  
Immune Tissues ◽  
Beta Lactoglobulin

The role of cholinergic neurons in mediating chloride secretion in anaphylaxis was assessed in muscle-stripped segments of distal colon from guinea pigs immunized to bovine milk. beta-Lactoglobulin evoked a concentration-dependent increase in short-circuit current (Isc) in immune, but not nonimmune, tissues. The Isc response to beta-lactoglobulin was reduced by piroxicam, pyrilamine, and cimetidine. Tetrodotoxin and atropine reduced the Isc response to beta-lactoglobulin in immune animals, whereas mecamylamine and ICS 205-930 were ineffective. beta-Lactoglobulin evoked a concentration-dependent increase in acetylcholine (ACh) release in immune, but not nonimmune, animals. In immune tissues after challenge with beta-lactoglobulin, ACh release paralleled the change in Isc. Piroxicam, cimetidine plus pyrilamine, or a combination of piroxicam, cimetidine, and pyrilamine significantly reduced the release of ACh after beta-lactoglobulin challenge. Histamine, dimaprit, and prostaglandins E2 evoked an increase in ACh release. These results suggest that beta-lactoglobulin releases prostaglandins and histamine probably from mast cells. Secretory responses that occur when immune animals are challenged with beta-lactoglobulin result, in part, from activation of cholinergic neurons that utilize muscarinic synapses for transfer of signals to the epithelium.

Role of protein kinase C-δ in the age-dependent secretagogue action of bile acids in mammalian colon

2007 ◽  
Vol 293 (6) ◽  
pp. C1851-C1861 ◽  
Author(s):  
Jainuch Kanchanapoo ◽  
Mei Ao ◽  
Roli Prasad ◽  
Christopher Moore ◽  
Cynthia Kay ◽  
...  
Keyword(s):  
Bile Acids ◽  
Short Circuit ◽  
Specific Inhibitor ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Specific Effects ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Do So

The role of specific PKC isoforms in the regulation of epithelial Cl− secretion by Ca2+-dependent secretagogues remains controversial. In the developing rabbit distal colon, the bile acid taurodeoxycholate (TDC) acts via intracellular calcium to stimulate Cl− transport in adult, but not in young, animals, whereas the PKC activator phorbol dibutyrate (PDB) stimulates Cl− transport at all ages. We tested the hypothesis that specific PKC isoforms account for the age-specific effects of TDC. The effects of conventional (cPKC) and novel (nPKC) PKC-specific inhibitors on TDC- and PDB-stimulated Cl− transport in adult and weanling colonocytes were assessed by using 6-methoxy-quinolyl acetoethyl ester. In adult colonocytes, the cPKC inhibitor Gö-6976 inhibited PDB action but not TDC action, whereas the cPKC and nPKC inhibitor Gö-6850 blocked both TDC and PDB actions. Additionally, rottlerin and the PKC-δ-specific inhibitor peptide (δV1-1) inhibited TDC- and PDB-stimulated Cl− transport in adult colonocytes. Rottlerin also decreased TDC-stimulated short-circuit current in intact colonic epithelia. Only Gö-6976, but neither rottlerin nor δV1-1, inhibited PDB-stimulated transport in weanling colonocytes. Colonic lysates express PKC-α, -λ, and -ι protein equally at all ages, but they do not express PKC-γ or -θ at any age. Expression of PKC-β and PKC-ε protein was newborn>adult>weanling, whereas PKC-δ was expressed in adult but not in weanling or newborn colonocytes. TDC (1.6-fold) and PDB (2.0-fold) stimulated PKC-δ enzymatic activity in adult colonocytes but failed to do so in weanling colonocytes. PKC-δ mRNA expression showed age dependence. Thus PKC-δ appears critical for the action of TDC in the adult colon, and its low expression in young animals may account for their inability to secrete in response to bile acids.

Inhibition of VIP-stimulated ion transport by a novel Y-receptor phenotype in rabbit distal colon

1993 ◽  
Vol 264 (5) ◽  
pp. G848-G854 ◽  
Author(s):  
G. H. Ballantyne ◽  
J. R. Goldenring ◽  
F. X. Fleming ◽  
S. Rush ◽  
J. S. Flint ◽  
...  
Keyword(s):  
Ion Transport ◽  
Colonic Mucosa ◽  
Peptide Yy ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ussing Chambers ◽  
Potent Inhibition ◽  
Colonic Secretion ◽  
Receptor Phenotype

Neurocrine, endocrine, and paracrine regulators are critical to the control of colonic secretion. These studies have investigated the inhibition of vasoactive intestinal polypeptide (VIP)-stimulated ion transport by peptide YY (PYY) and other Y-class effectors in rabbit distal colonic mucosa mounted in Ussing chambers. PYY decreased basal short-circuit current (Isc) but did not significantly change either basal Na+ or Cl- flux. PYY inhibited VIP-stimulated increases in Isc by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generated increases in Isc by a tetrodotoxin-insensitive mechanism. PYY inhibited cholera toxin-stimulated as well as forskolin-stimulated increases in Isc but failed to alter stimulation by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increases in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PYY, neuropeptide Y (NPY), (Leu31,Pro34)-NPY, and pancreatic polypeptide (PP) all demonstrated potent inhibition of VIP-stimulated increases in Isc. PYY-(13-36) demonstrated little effect on VIP stimulation. Thus the rabbit distal colon possesses a novel Y-class receptor phenotype that demonstrates high affinity for all three PP-fold peptides, NPY, PYY, and PP.

Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion

1995 ◽  
Vol 269 (3) ◽  
pp. G346-G351 ◽  
Author(s):  
M. Sidhu ◽  
H. J. Cooke
Keyword(s):  
Muscarinic Receptors ◽  
Guinea Pigs ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Submucosal Plexus ◽  
Reflex Pathways ◽  
Colonic Secretion ◽  
Serotoninergic Receptors

Neural reflex pathways activated in response to mucosal stroking were investigated in segments of distal colon from guinea pigs. Stroking the mucosal surface of whole thickness or muscle-stripped segments with a brush at 1/s evoked an increase in short-circuit current (Isc) whose duration and amplitude were dependent on the number of strokes. The increase in Isc induced by mucosal stroking was virtually abolished by inhibitors of chloride secretion and by tetrodotoxin. The response was reduced by atropine, renzapride, and N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide but not by mecamylamine, ketanserin, tropisetron, or SDZ-205-557. Mucosal application of 5-hydroxytryptamine and 5-hydroxyindalpine increased Isc, which was attenuated by tetrodotoxin and renzapride. The results suggest that mucosal stroking evokes chloride secretion by activating neural reflex pathways utilizing serotoninergic receptors, of the 5-HT1P class, as well as muscarinic receptors within the submucosal plexus.

Epithelial responses evoked by stimulation of submucosal neurons in guinea pig distal colon

1987 ◽  
Vol 252 (5) ◽  
pp. G667-G674 ◽  
Author(s):  
A. Kuwahara ◽  
S. Bowen ◽  
J. Wang ◽  
C. Condon ◽  
H. J. Cooke
Keyword(s):  
Guinea Pig ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Flux ◽  
Positive Currents ◽  
Release Of Acetylcholine ◽  
Set Up ◽  
Short Circuit Currents ◽  
Stimulation Of

The influence of submucosal neurons on ion transport in the guinea pig distal colon was examined in muscle-stripped sheets of submucosa-mucosa set up in Ussing flux chambers. Spontaneous variations in potential differences (PD) and short-circuit current occurred ranging from positive currents associated with luminal negative PDs to negative currents with luminal positive PDs. Basal current in both groups was reduced by mucosal amiloride. In tissues with positive or negative short-circuit currents, unidirectional mucosal-to-serosal sodium fluxes were greater than serosal-to-mucosal fluxes and small net absorptive fluxes were present. Little or no chloride secretory flux was present. Electrical stimulation of submucosal neurons evoked a tetrodotoxin-sensitive increase in short-circuit current in tissues with positive or negative short-circuit currents. This was due to an increase in net chloride flux and little change in net sodium flux or residual flux. The increase in net chloride flux was due almost entirely to an increase in serosal-to-mucosal chloride flux and was associated with an increase in total tissue conductance. The stimulus-evoked response was reduced by atropine. These results suggest that stimulation of submucosal neurons that innervate the distal colonic epithelium evokes a large chloride secretory response that is due in part to release of acetylcholine at neuro-enterocyte junctions.

Enhancement of the performance of CdS/CdTe heterojunction solar cell using TiO2/ZnO bi-layer ARC and V2O5 BSF layers: A simulation approach

2020 ◽  
Vol 92 (2) ◽  
pp. 20901
Author(s):  
Abdul Kuddus ◽  
Md. Ferdous Rahman ◽  
Jaker Hossain ◽  
Abu Bakar Md. Ismail
Keyword(s):  
Solar Cell ◽  
Short Circuit ◽  
Photovoltaic Performance ◽  
Short Circuit Current ◽  
Short Circuit Current Density ◽  
Open Circuit ◽  
Heterojunction Solar Cell ◽  
Back Surface ◽  
Heterojunction Solar Cells

This article presents the role of Bi-layer anti-reflection coating (ARC) of TiO2/ZnO and back surface field (BSF) of V2O5 for improving the photovoltaic performance of Cadmium Sulfide (CdS) and Cadmium Telluride (CdTe) based heterojunction solar cells (HJSCs). The simulation was performed at different concentrations, thickness, defect densities of each active materials and working temperatures to optimize the most excellent structure and working conditions for achieving the highest cell performance using obtained optical and electrical parameters value from the experimental investigation on spin-coated CdS, CdTe, ZnO, TiO2 and V2O5 thin films deposited on the glass substrate. The simulation results reveal that the designed CdS/CdTe based heterojunction cell offers the highest efficiency, η of ∼25% with an enhanced open-circuit voltage, Voc of 0.811 V, short circuit current density, Jsc of 38.51 mA cm−2, fill factor, FF of 80% with bi-layer ARC and BSF. Moreover, it appears that the TiO2/ZnO bi-layer ARC, as well as ETL and V2O5 as BSF, could be highly promising materials of choice for CdS/CdTe based heterojunction solar cell.

Protein kinase C potentiates cAMP-stimulated mouse duodenal mucosal bicarbonate secretion in vitro

2004 ◽  
Vol 286 (5) ◽  
pp. G814-G821 ◽  
Author(s):  
Bi-Guang Tuo ◽  
Jimmy Y. C. Chow ◽  
Kim E. Barrett ◽  
Jon I. Isenberg
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Duodenal Mucosa ◽  
Bicarbonate Secretion ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ussing Chambers ◽  
Duodenal Bicarbonate Secretion

PKC has been shown to regulate epithelial Cl- secretion in a variety of models. However, the role of PKC in duodenal mucosal bicarbonate secretion is less clear. We aimed to investigate the role of PKC in regulation of duodenal mucosal bicarbonate secretion. Bicarbonate secretion by murine duodenal mucosa was examined in vitro in Ussing chambers using a pH-stat technique. PKC isoform expression and activity were assessed by Western blotting and in vitro kinase assays, respectively. PMA (an activator of PKC) alone had no effect on duodenal bicarbonate secretion or short-circuit current ( Isc). When PMA and dibutyryl-cAMP (db-cAMP) were added simultaneously, PMA failed to alter db-cAMP-stimulated duodenal bicarbonate secretion or Isc ( P > 0.05). However, a 1-h preincubation with PMA potentiated db-cAMP-stimulated duodenal bicarbonate secretion and Isc in a concentration-dependent manner (from 10-8 to 10-5M) ( P < 0.05). PMA preincubation had no effects on carbachol- or heat-stable toxin-stimulated bicarbonate secretion. Western blot analysis revealed that PKCα, -γ, -ϵ, -θ, -μ, and -ι/λ were expressed in murine duodenal mucosa. Ro 31–8220 (an inhibitor active against PKCϵ, -α, -β, and -γ), but not Gö 6983 (an inhibitor active against PKCα, -γ, -β, and -δ), reversed the potentiating effect of PMA on db-cAMP-stimulated bicarbonate secretion. PMA also time- and concentration-dependently increased the activity of PKCϵ, an effect that was prevented by Ro 31–8220 but not Gö 6983. These results demonstrate that activation of PKC potentiates cAMP-stimulated duodenal bicarbonate secretion, whereas it does not modify basal secretion. The effect of PKC on cAMP-stimulated bicarbonate secretion is mediated by the PKCϵ isoform.

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